Converging evidence indicates that concern about weight gain after abstinence increases reluctance to attempt smoking cessation, and that post-cessation weight gain is associated with smoking relapse. Chronic smoking causes numerous neurobiological changes, and smoking abstinence is associated with changes in appetite. Elucidating biobehavioral mechanisms associated with these effects of abstinence is critical in identifying those at high risk for weight gain and for planning appropriate treatment contingencies. The long-term goal of our research is to delineate the interactions of neurobiological mechanisms responsible for appetite regulation and tobacco addiction. The specific goal of this project is to determine the extent to which levels of appetite-regulating peptides (i.e., leptin, ghrelin, GLP-1, neuropeptide Y, and orexin) measured during smoking and during the early phase of abstinence predict subsequent changes in appetite, dietary intake, weight, and relapse during smoking cessation. We will also examine the extent to which abstinence-induced blunted adrenocortical and cardiovascular responses to stress predict changes in appetite, dietary intake, weight, and relapse over the first three months of a cessation attempt. This application is a continuation of our focused program investigating the role of stress in smoking relapse while taking into account that the effects of stress do not operate in vacuum, and that there is a need to clearly identify interactions of stress effects with other motivational and mood states. We have completed studies identifying specific psychobiological patterns of the stress response sensitive to individual and situational factors in smokers and non-smokers. We recently completed a series of studies that examined changes in hypothalamic-pituitary- adrenocortical responses to stress following short-term smoking abstinence and evaluated the extent to which these changes predict early relapse. The composite work and literature have provided relevant directions to guide the development of the proposed program. PUBLIC HEALTH RELEVANCE: Tobacco addiction/dependence is the leading preventable cause of cancer and cardiovascular diseases. Evidence indicates that weight gain occurring after smoking abstinence increases reluctance to attempt smoking cessation, especially among women. There is also evidence that post-cessation weight gain is associated with smoking relapse. We plan to determine the extent to which changes in appetite-related peptides and stress response during early abstinence predict subsequent weight gain and smoking relapse. Gaining a better understanding of these factors will be essential in designing interventions to address weight gain and stress effects during cessation, and to subsequently reduce smoking relapse rates. Reducing smoking relapse will have a direct public health impact in reducing the burden of smoking-related diseases.